ABSTRACT Smoking remains the leading preventable cause of morbidity and mortality in the d United States and its prevalence is elevated in disparate groups (e.g., mental health problems, low education, low SES) characterized by chronic stress. Integrated physiological and psychological processes related to stress and cigarette smoking may elucidate these relations. For example, nicotine consumption and stress repeatedly activate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) system, leading to dysregulation that has been empirically linked to craving, reward, and lapse, following cessation. Emerging research suggests cognitive vulnerabilities related to how one appraises stress also may play a role in stress- precipitated smoking. However, one notable gap in the existing body of work is that it has not adequately bridged the relations between psychological states, physiology, and smoking behavior, thereby limiting the utility of translating findings to intervention. The Biopsychosocial model of challenge and threat identifies two distinct responses to stress, integrating psychological and physiological processes. Specifically, a challenge appraisal, in the context of stress, occurs when one perceives coping resources to exceed environmental demands, and is accompanied by less negative affect. Alternatively, a threat appraisal occurs when one perceives limited resources to cope with a taxing environmental demand and is accompanied by high negative affect and inability to respond in an adaptive manner. These responses are also associated with unique cardiovascular responses whereby both responses are associated with increased sympathetic nervous system activation but challenge is characterized by an increase in cardiac output (CO) and decrease in total peripheral resistance (TPR), and threat is prototypically characterized by little change in CO and an increase in TPR. Informed by this model, the current proposal seeks to fill an existing gap in the investigation of stress- precipitated smoking by simultaneously examining cognitive appraisal and cardiovascular reactivity as mechanisms explaining stress-precipitated smoking. Using a modified version of the Trier Social Stress Test, participants will be randomly assigned to receive either supportive (i.e., positive) or unsupportive (i.e., negative) non-verbal feedback from confederates. We expect two significant outcomes from the proposed research: (1) determine whether challenge and threat manipulations are differentially related to smoking motivation and smoking behavior; and (2) identify cognitive appraisal and CV reactivity as mechanisms explaining stress-precipitated smoking, thereby providing preliminary support for the development and application of interventions. Via this novel exploration of stress-precipitated smoking, and multi-method examination of cognitive and physiological explanatory mechanisms, this proposal is expected to have direct translational impact on smoking intervention.